Some 53,000 fans at the Wanda Metropolitano stadium roared with excitement as they welcomed to the stage the original band members Mick Jagger, 78, and guitarists Keith Richards, 78, and Ronnie Wood, who turned 75 on Wednesday.
They have been joined by drummer Steve Jordan for the tour, titled SIXTY. Watts, who joined the band in 1963, died last year aged 80.
"Hola Madrid!" shouted the band's frontman Jagger to even louder cheering after the band opened the show with Street Fighting Man and Jagger launched into his signature strut dance moves.
Before the first song, videos of Watts where displayed in big screens on the stage and the band gave an emotional tribute to their late friend.
"This is our first European tour without Charlie. We miss him a lot," said Jagger in Spanish right before playing Sad, Sad, Sad to a moved crowd.
"The band dedicated the show to him," show designer Patrick Woodroffe, who has worked with the Stones for four decades, told Reuters.Â
"Some time has gone past and we miss him all the time, we laugh about him, we talk about him a lot and this is a way to celebrate his life rather than to mourn it."
As part of their 17 songs, the band played Gimme Shelter as the Ukrainian flag and footage of destroyed Ukrainian cities where displayed on the monitors as a statement against war.
During the 14-show tour, the British band will play stadiums and arenas in 10 countries, including their homeland.
The Stones will next play in Munich on Sunday and later perform in Liverpool, Amsterdam, Bern, Milan, London, Brussels, Vienna, Paris and Stockholm.
According to Woodroffe, the Stones have no plans to stop rolling, saying: "I can tell you categorically that The Rolling Stones will never do a farewell tour."
